Newborn screening programs have been established to quantify the level of metabolites associated with treatable diseases. Mucopolysaccharidosis type I (MPS-I) is a lysosomal storage disorder caused by the deficiency of α-L-iduronidase (IdA; EC 3.2.1.76) enzymatic activity and can manifest three major clinical phenotypes: Hurler, Scheie, and Hurler-Scheie syndromes.
IdA is essential for the degradation of the glycosaminoglycans dermatan and heparan sulfate within lysosomes. Failure to breakdown these polysaccharides causes physical changes such as joint stiffness, skeletal abnormalities, and corneal clouding. Hurler syndrome is characterized by valvular heart disease, mental deterioration, and death in childhood. As symptoms may not be recognized early in life, the diagnosis of MPS-I is a challenging task. Enzyme replacement therapy and bone marrow transplantation have been developed for this disease, and both are beneficial if performed early. Because early detection is necessary for optimum clinical response to therapy, the need for developing screens for the early recognition of MPS-I is of great interest.
Tandem mass spectrometry (tandem MS or MSMS) is one platform for measuring disease-associated enzyme activities using rehydrated dried blood spots (DBS) for the quantitative measurement of the activities of enzymes responsible for several lysosomal storage disorders. In addition to electrospray ionization tandem mass spectrometry (ESI-MSMS) assays, fluorometric and radiometric assays for α-L-iduronidase have been developed.
Treatments now available for MPS-I require early detection for optimum clinical response to therapy. Accordingly, there exists a need for methods for newborn screening of the activity of the relevant enzyme, α-L-iduronidase. The present invention fulfills this need and provides further related advantages.